Total syntheses of glucosidase inhibitors, cyclophellitols

Kuniaki Tatsuta, Yoshihisa Niwata, Kazuo Umezawa, Kazunobu Toshima, Masaya Nakata

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.

Original languageEnglish
Pages (from-to)189-203
Number of pages15
JournalCarbohydrate Research
Volume222
Issue numberC
DOIs
Publication statusPublished - 1991 Dec 30

Fingerprint

Glucosidases
Nitriles
Cycloaddition
Cycloaddition Reaction
Oxides
Heptanes
Hydrogenolysis
Oximes
Glycoside Hydrolases
Epoxy Compounds
Alkenes
Galactose
Glucose
cyclophellitol
methyl-galactopyranoside

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry

Cite this

Total syntheses of glucosidase inhibitors, cyclophellitols. / Tatsuta, Kuniaki; Niwata, Yoshihisa; Umezawa, Kazuo; Toshima, Kazunobu; Nakata, Masaya.

In: Carbohydrate Research, Vol. 222, No. C, 30.12.1991, p. 189-203.

Research output: Contribution to journalArticle

Tatsuta, Kuniaki ; Niwata, Yoshihisa ; Umezawa, Kazuo ; Toshima, Kazunobu ; Nakata, Masaya. / Total syntheses of glucosidase inhibitors, cyclophellitols. In: Carbohydrate Research. 1991 ; Vol. 222, No. C. pp. 189-203.
@article{86b1e75f47a84a769535284f0cbf9c56,
title = "Total syntheses of glucosidase inhibitors, cyclophellitols",
abstract = "A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.",
author = "Kuniaki Tatsuta and Yoshihisa Niwata and Kazuo Umezawa and Kazunobu Toshima and Masaya Nakata",
year = "1991",
month = "12",
day = "30",
doi = "10.1016/0008-6215(91)89017-A",
language = "English",
volume = "222",
pages = "189--203",
journal = "Carbohydrate Research",
issn = "0008-6215",
publisher = "Elsevier BV",
number = "C",

}

TY - JOUR

T1 - Total syntheses of glucosidase inhibitors, cyclophellitols

AU - Tatsuta, Kuniaki

AU - Niwata, Yoshihisa

AU - Umezawa, Kazuo

AU - Toshima, Kazunobu

AU - Nakata, Masaya

PY - 1991/12/30

Y1 - 1991/12/30

N2 - A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.

AB - A β-d-glucosidase inhibitor, cyclophellitol [(1S,2R,3S,4R,5R,6R)-5-hydroxymethyl-7-oxabicyclo[4.1.0]heptane-2,3,4-triol, 1] and its epoxide diastereomer, 1,6-epicyclophellitol (2) have been synthesized by using an intramolecular [3+2]-cycloaddition of a nitrile oxide to an alkene as a key step. 2,3,4-Tri-O-benzyl-6,7-dideoxy-d-ido-hept- 6-enose (E,Z)-oxime (6) was prepared from l-glucose in 11 steps. Intramolecular cycloaddition of 6 was realized by NaOCl via an intermediary nitrile oxide to afford the isoxazoline, (1S,2R,3S,4S,5R)-3,4,5-tribenzyloxy-2-hydroxy-8-oxa-7-azabicyclo[4.3.0]non-6-ene (7). Hydrogenolysis of 7 followed by a 5-step sequence gave cyclophellitol (1). Compound 2 was synthesized from methyl δ-d-galactopyranoside by using a conceptually similar route. The glycosidase-inhibiting activities of 2 were examined.

UR - http://www.scopus.com/inward/record.url?scp=0026332029&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026332029&partnerID=8YFLogxK

U2 - 10.1016/0008-6215(91)89017-A

DO - 10.1016/0008-6215(91)89017-A

M3 - Article

AN - SCOPUS:0026332029

VL - 222

SP - 189

EP - 203

JO - Carbohydrate Research

JF - Carbohydrate Research

SN - 0008-6215

IS - C

ER -